In Vitro Characterization of a Liposomal Formulation of Celecoxib Containing 1,2-Distearoyl-sn-Glycero-3-Phosphocholine, Cholesterol, and Polyethylene Glycol and its Functional Effects Against Colorectal Cancer Cell Lines


ERDOG A., Limasale Y. D. P., KESKİN D., TEZCANER A., BANERJEE S.

JOURNAL OF PHARMACEUTICAL SCIENCES, vol.102, no.10, pp.3666-3677, 2013 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 102 Issue: 10
  • Publication Date: 2013
  • Doi Number: 10.1002/jps.23674
  • Journal Name: JOURNAL OF PHARMACEUTICAL SCIENCES
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.3666-3677
  • Keywords: liposome, celecoxib, colon, cancer, drug delivery systems, nanoparticles, pegylation, NONSTEROIDAL ANTIINFLAMMATORY DRUGS, COX-2 INHIBITORS, INTRACELLULAR FATE, BREAST-CANCER, SOLID TUMORS, DELIVERY, VIVO, PHOSPHOLIPIDS, EXPRESSION, APOPTOSIS
  • Middle East Technical University Affiliated: Yes

Abstract

Nanosized liposomal drug delivery systems are well suited for selective drug delivery at tumor sites. Celecoxib (CLX) is a highly hydrophobic cyclooxygenase-2 inhibitor that can reduce the incidence of colorectal polyps; however, the adverse cardiovascular effects limit its applicability. Here, we report a liposomal formulation of CLX using 1,2-Distearoyl-sn-glycero-3-phosphocholine, cholesterol, and polyethylene glycol. Encapsulation efficiency of the drug was greater than 70%; the release was slow and sustained with only 12%-20% of CLX released in the first 12h. Flow cytometry and confocal microscopy studies using the colon cancer cell lines HCT-116 and SW620 showed significantly higher cellular association and internalization of the liposomes after incubation for 6h when compared with 30min. The liposomes did not colocalize with transferrin, but had a punctuate appearance, indicating vesicular localization. Cell proliferation was inhibited by 95% and 78%, respectively, in SW620 and HT29 cells after incubation with 600M liposomal CLX for 72h. Moreover, cellular motility, as shown by a scratch wound healing assay, was also significantly (p=0.006) inhibited when SW620 cells were incubated with 400M liposomal CLX. This is the first report of the successful encapsulation of CLX in a long-circulating liposomal formulation that could be effective against colorectal cancer. (c) 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:3666-3677, 2013